(1S)-1-[4-fluoro-2-(3-methylphenyl)phenyl]-5-methoxy-1-[(3R)-piperidin-3-yl]pentan-1-ol | 1219939-26-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S)-1-[4-fluoro-2-(3-methylphenyl)phenyl]-5-methoxy-1-[(3R)-piperidin-3-yl]pentan-1-ol
• CAS: 1219939-26-0
• 化学式: C₂₄H₃₂FNO₂
• 分子量: 385.522
• InChiKey: YUJXPBSPCFSNHB-YKSBVNFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S)-1-[4-fluoro-2-(3-methylphenyl)phenyl]-5-methoxy-1-[(3R)-piperidin-3-yl]pentan-1-ol 、 (1S,3R,4S)-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-hydroxycyclopentanecarboxylic acid 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成
  参考文献：
  名称：

  Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket

  摘要：

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.043
• 作为产物：
  描述：

  (3R)-3-[(甲氧基甲基氨基)羰基]-1-哌啶羧酸 1,1-二甲基乙酯 在 盐酸 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 48.0h， 生成 (1S)-1-[4-fluoro-2-(3-methylphenyl)phenyl]-5-methoxy-1-[(3R)-piperidin-3-yl]pentan-1-ol
  参考文献：
  名称：

  Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket

  摘要：

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.043

文献信息

• [EN] RENIN INHIBITORS<br/>[FR] INHIBITEURS DE LA RÉNINE
  申请人：VITAE PHARMACEUTICALS INC

  公开号：WO2007117559A2

  公开（公告）日：2007-10-18

  (EN) Described are compounds of the formula ( I ) which are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also described are methods of use of the compounds described herein in ameliorating or treating aspartic protease related disorders in a subject in need thereof.(FR) L'invention concerne des composés actifs oralement et qui se lient à des protéases aspartiques, de manière à inhiber leur activité. Lesdits composés sont utilisés dans le traitement ou l'amélioration de maladies associées à l'activités des protéases aspartiques. L'invention concerne également des procédés d'utilisation des composés spécifiés dans la description, permettant l'amélioration ou le traitement de troubles liés aux protéases aspartiques chez un sujet nécessitant ces soins.
• Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket
  作者：Jing Yuan、Robert D. Simpson、Wei Zhao、Colin M. Tice、Zhenrong Xu、Salvacion Cacatian、Lanqi Jia、Patrick T. Flaherty、Joan Guo、Alexey Ishchenko、Zhongren Wu、Brian M. McKeever、Boyd B. Scott、Yuri Bukhtiyarov、Jennifer Berbaum、Reshma Panemangalore、Ross Bentley、Christopher P. Doe、Richard K. Harrison、Gerard M. McGeehan、Suresh B. Singh、Lawrence W. Dillard、John J. Baldwin、David A. Claremon

  DOI：10.1016/j.bmcl.2011.06.043

  日期：2011.8

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.